PT  - JOURNAL ARTICLE
AU  - Martins, Raquel R.
AU  - Rera, Michael
AU  - Henriques, Catarina M.
TI  - TRANSCRIPTOMIC SIGNATURES OF TELOMERASE-DEPENDENT AND -INDEPENDENT AGEING, IN THE ZEBRAFISH GUT AND BRAIN
AID  - 10.1101/2022.05.24.493215
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.05.24.493215
4099  - http://biorxiv.org/content/early/2022/05/26/2022.05.24.493215.short
4100  - http://biorxiv.org/content/early/2022/05/26/2022.05.24.493215.full
AB  - Telomerase is best known for its role in the maintenance of telomere length and its implications for ageing and cancer. The mechanisms, kinetics and tissue-specificity underlying the protective or deleterious mechanisms of telomerase, however, remain largely unknown. Here, we sought to determine the telomerase-dependent and -independent transcriptomic changes with ageing, in the gut and brain, as examples of high and low proliferative tissues, respectively. We hypothesised this could shed light on common telomerase-dependent and -independent therapeutic targets aimed at preventing or ameliorating age-associated dysfunction in both tissues. For this, we used the zebrafish model which, similarly to humans, depends on telomerase for health-and lifespan. We performed whole tissue RNA sequencing of gut and brain, in naturally aged zebrafish alongside prematurely aged telomerase null mutants (tert-/-), throughout their lifespan. Our study highlights stem cell exhaustion as the first main hallmark of ageing to be de-regulated in WT zebrafish gut and brain. Towards the end of life, altered intercellular communication becomes the main hallmark of ageing de-regulated in both gut and brain, and this is accelerated in both tissues, in the absence of telomerase. Finally, we identify 7 key gene changes common between the gut and brain at the early stages of ageing, highlighting potential early intervention therapeutic targets for preventing age-associated dysfunction in both tissues.Competing Interest StatementThe authors have declared no competing interest.